A genetic disorder of cholesterol transport named for
the secluded island of Tangier, off the coast of Virginia.
Characteristically, patients present orange tonsils, very low levels of
high-density lipoprotein (HDL), and enlarged liver and spleen.
High-Density Lipoprotein (HDL) Deficiency;
Although the molecular basis remains unknown,
a mutation in the ABC1 (ATP-binding cassette) gene on chromosome 9q31 has
been reported. ABC1 codes for a protein that helps rid cells of excess
cholesterol. Autosomal codominant disorder. Heterozygotes do not have any
The primary problem appears to be a defect in cell
signaling and in mobilization of cellular lipids, leading to intracellular
cholesterol esters accumulation. This defect is compounded by a low plasma
concentration of apolipoprotein A-I (an essential component of HDL) caused
by a pathologically rapid catabolism. This results in a low level of HDL in
plasma, making it unable to scavenge cholesterol from tissues. Tissues that
accumulate excessive cholesterol include tonsils, liver, spleen, lymph
nodes, thymus, intestines, and peripheral nerves. Histology reveals deposits
of cholesterol esters outside of lysosomes in the cytoplasm.
Homozygotes have a marked deficiency of HDL cholesterol
and apolipoprotein (apo) A-I levels (both <10 mg/dL), decreased low-density
lipoprotein (LDL) cholesterol levels (about 40% of normal), and mild
Large orange tonsils, splenomegaly, neuropathy,
and rectal mucosal changes (orange-brown spots). Neuropathy may include
demyelination (mononeuropathic or polyneuropathic) and axonal degeneration
with a syringomyelic (dissociative) picture. Sensory loss may lead to global
anesthesia but autonomic neuropathy has not been described. Unlike earlier
beliefs, it is now known that the risk of atherosclerosis is increased in
older patients. Mitral and pulmonary valve abnormalities have been reported.
Loss of vision, incomplete eyelid closure. May have abnormal platelet
The possibility of an association with cerebellar dysgenesis, cardiac defects and
renal anomalies has been reported. Also, few case reports of annual pancreatic
defect have been suggested.
There is no specific treatment, although dietary fat restrictions
Anemia and hemolysis,
thrombocytopenia (prolonged bleeding time correctable with desmopressin
acetate). Sleep apnea (airway obstruction). Liver function tests,
electrolytes (malabsorption). ECG, echocardiogram, stress test/coronary
angiography if ischemia suspected. Evaluate extent of neurological deficit,
cranial nerve palsy (upper airway reflexes).
Rapid sequence induction
is recommended if upper airway
reflexes are lost. Complete airway obstruction is possible if tonsils are
“kissing” (use nasopharyngeal airway to relieve). Meticulous positioning
with adequate padding during surgery and recovery. Regional techniques are
relatively contraindicated in the presence of neuropathy. Management depends
upon systemic manifestations of the disease, such as ischemic heart disease.
The presence of neuropathies or muscle weakness requires cautious use of
muscle relaxants and patient positioning. Regional techniques should be
avoided in the presence of neuropathy or platelet dysfunction. Care should
be taken to protect the eyes.
Avoid succinylcholine if neuropathy
is present (risk of hyperkalemia). Reduce the dosage of nondepolarizing
muscle-relaxant drugs in patients with extensive neuropathy or muscle
weakness. Use of muscle relaxants should be guided by neuromuscular
monitoring. If sleep apnea is ...